Our hypothesis is that fundamental opiate signaling processes exist and evolved in invertebrate neural tissues and have been evolutionarily retained in humans. This is supported by our preliminary findings that invertebrates produce an endogenous morphine-like material and have mu3 opiate receptors which are indistinguishable from the human counterpart. The experiments in this proposal are designed to identify morphine itself, clone the mu3 receptor in the invertebrate nervous system and directly relate these findings to a function test, i.e., morphine stimulated calcium transients. We propose to address the following objectives: What is the role of the opiate alkaloid, i.e., morphine in the invertebrate nervous system and what does it tell us about the human system? The experiments in this proposal are designed to answer these questions. We propose to develop this hypothesis with the neural tissues of the marine bivalve Mytilus edulis, making it a model for this analysis. More specifically, these studies test our hypothesis that opiate signaling, transcending pain functions, evolved in invertebrates to diminish sensory inputs, and that because this system worked so well, it was retained during evolution. Given this growing documentation for endogenous morphine in neural signaling the potential for its involvement in psychiatry is becoming evident.